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Tissue-specific postprandial clearance is the major determinant of PPARgamma-induced triglyceride lowering in the rat.
Am J Physiol Regul Integr Comp Physiol. 2009 Jan; 296(1):R57-66.AJ

Abstract

Peroxisome proliferator-activated receptor-gamma (PPARgamma) agonism potently reduces circulating triglycerides (TG) in rodents and more modestly so in humans. This study aimed to quantify in vivo the relative contribution of hepatic VLDL-TG secretion and tissue-specific TG clearance to such action. Rats were fed an obesogenic diet, treated with the PPARgamma full agonist COOH (30 mg.kg(-1).day(-1)) for 3 wk, and studied in both the fasted and refed (fat-free) states. Hepatic VLDL-TG secretion rate was not affected by chronic COOH in the fasted state and was only modestly decreased (-30%) in refed rats. In contrast, postprandial VLDL-TG clearance was increased 2.6-fold by COOH, which concomitantly stimulated adipose tissue TG-derived lipid uptake and one of its major determinants, lipoprotein lipase (LPL) activity, in a highly depot-specific manner. TG-derived lipid uptake and LPL were indeed strongly increased in subcutaneous inguinal white adipose tissue and in brown adipose tissue, independently of the nutritional state, whereas of the three visceral fat depots examined (epididymal, retroperitoneal, mesenteric) only the latter responded consistently to COOH. Robust correlations (0.5 < r < 0.9) were observed between TG-derived lipid uptake and LPL in adipose tissues. The agonist did not increase LPL in muscle, and its enhancing action on postprandial muscle lipid uptake appeared to be mediated by post-LPL processes involving increased expression of fatty acid binding/transport proteins (aP2, likely in infiltrated adipocytes, FAT/CD36, and FATP-1). The study establishes in a diet-induced obesity model the major contribution of lipid uptake by specific, metabolically safe adipose depots to the postprandial hypotriglyceridemic action of PPARgamma agonism, and suggests a key role for LPL therein.

Authors+Show Affiliations

Laval Hospital Research Center, Faculty of Medicine, Laval Univ., 2725 Ch Sainte-Foy, Québec, QC, Canada G1V 4G5.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18971352

Citation

Laplante, Mathieu, et al. "Tissue-specific Postprandial Clearance Is the Major Determinant of PPARgamma-induced Triglyceride Lowering in the Rat." American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, vol. 296, no. 1, 2009, pp. R57-66.
Laplante M, Festuccia WT, Soucy G, et al. Tissue-specific postprandial clearance is the major determinant of PPARgamma-induced triglyceride lowering in the rat. Am J Physiol Regul Integr Comp Physiol. 2009;296(1):R57-66.
Laplante, M., Festuccia, W. T., Soucy, G., Blanchard, P. G., Renaud, A., Berger, J. P., Olivecrona, G., & Deshaies, Y. (2009). Tissue-specific postprandial clearance is the major determinant of PPARgamma-induced triglyceride lowering in the rat. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 296(1), R57-66. https://doi.org/10.1152/ajpregu.90552.2008
Laplante M, et al. Tissue-specific Postprandial Clearance Is the Major Determinant of PPARgamma-induced Triglyceride Lowering in the Rat. Am J Physiol Regul Integr Comp Physiol. 2009;296(1):R57-66. PubMed PMID: 18971352.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tissue-specific postprandial clearance is the major determinant of PPARgamma-induced triglyceride lowering in the rat. AU - Laplante,Mathieu, AU - Festuccia,William T, AU - Soucy,Geneviève, AU - Blanchard,Pierre-Gilles, AU - Renaud,Alexandra, AU - Berger,Joel P, AU - Olivecrona,Gunilla, AU - Deshaies,Yves, Y1 - 2008/10/29/ PY - 2008/10/31/pubmed PY - 2009/2/7/medline PY - 2008/10/31/entrez SP - R57 EP - 66 JF - American journal of physiology. Regulatory, integrative and comparative physiology JO - Am. J. Physiol. Regul. Integr. Comp. Physiol. VL - 296 IS - 1 N2 - Peroxisome proliferator-activated receptor-gamma (PPARgamma) agonism potently reduces circulating triglycerides (TG) in rodents and more modestly so in humans. This study aimed to quantify in vivo the relative contribution of hepatic VLDL-TG secretion and tissue-specific TG clearance to such action. Rats were fed an obesogenic diet, treated with the PPARgamma full agonist COOH (30 mg.kg(-1).day(-1)) for 3 wk, and studied in both the fasted and refed (fat-free) states. Hepatic VLDL-TG secretion rate was not affected by chronic COOH in the fasted state and was only modestly decreased (-30%) in refed rats. In contrast, postprandial VLDL-TG clearance was increased 2.6-fold by COOH, which concomitantly stimulated adipose tissue TG-derived lipid uptake and one of its major determinants, lipoprotein lipase (LPL) activity, in a highly depot-specific manner. TG-derived lipid uptake and LPL were indeed strongly increased in subcutaneous inguinal white adipose tissue and in brown adipose tissue, independently of the nutritional state, whereas of the three visceral fat depots examined (epididymal, retroperitoneal, mesenteric) only the latter responded consistently to COOH. Robust correlations (0.5 < r < 0.9) were observed between TG-derived lipid uptake and LPL in adipose tissues. The agonist did not increase LPL in muscle, and its enhancing action on postprandial muscle lipid uptake appeared to be mediated by post-LPL processes involving increased expression of fatty acid binding/transport proteins (aP2, likely in infiltrated adipocytes, FAT/CD36, and FATP-1). The study establishes in a diet-induced obesity model the major contribution of lipid uptake by specific, metabolically safe adipose depots to the postprandial hypotriglyceridemic action of PPARgamma agonism, and suggests a key role for LPL therein. SN - 0363-6119 UR - https://www.unboundmedicine.com/medline/citation/18971352/Tissue_specific_postprandial_clearance_is_the_major_determinant_of_PPARgamma_induced_triglyceride_lowering_in_the_rat_ L2 - http://www.physiology.org/doi/full/10.1152/ajpregu.90552.2008?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -